Surgical repair or replacement of major blood vessels or heart valves damaged by disease or injury is a difficult and delicate process. Where the blood vessel or valve involved has been damaged or has deteriorated to the point where it cannot be repaired, it must be replaced.
With respect to blood vessels, techniques have been developed to use arteries or veins from other parts of the patient's body, or from a donor, to substitute for the damaged or diseased body part. This results in a duality of required surgical procedures wherein a length of vessel suitable for replacing the injured or diseased portion is removed from one part of the body, or from the donor, and implanted at the site of the injury or disease.
The use of blood vessels from donors has been successfully carried out, but such procedures call for the suppression of the body's normal immune system antagonism toward the presence of foreign tissue. Although this procedure has become safer and more readily regulated, it requires drugs which may have untoward side effects on the patient. Certainly, the simpler and more straightforward a surgical procedure, the greater the likelihood that the patient will tolerate it well and will make a satisfactory recovery.
More recently, artificial shunts, grafts, patches and heart valves have been developed to be surgically implanted to replace those found to be damaged or defective. Such artificial expedients have been made from materials selected for their capacity to be tolerated well by the human body, to handle the requirements of fluid pressures demanded of the affected blood vessel or valve, and to provide attachment sites for the anchoring of sutures and the formation of scar tissue. Among such materials are tetrafluoroethylene (sold under the registered trademark "Teflon") and polyethylene glycol terephthalate (sold under the registered trademark "Dacron"). Both are especially well-suited for producing knitted, woven or braided implants, grafts, or attachment cuffs. Another material so used for shunts, grafts and patches is an expanded microporous polytetrafluoroethylene sold under the registered trademark "Gore-Tex".
Examples of such an artificial heart valve are the valves manufactured by St. Jude Medical and Edwards CVS Division of Baxter Healthcare, Inc. The Edwards valve assembly consists generally of a rigid, rounded metallic valve body or frame within which a metallic valve plate or leaflet is rotatably suspended. A cuff or attachment ring fashioned from one of the materials described above surrounds the valve frame and provides an attachment site for fibrous tissue to infiltrate and anchor the valve assembly in place. The valve plate is shaped and pivoted to act as a check valve against the backflow of blood, and is thus in intimate contact with the stream of blood passing to or from the heart. A similar construction is utilized in the heart valve sold under the St. Jude Medical registered trademark. This valve utilizes a pair of leaflets as the blood flow regulators.
Examples of vascular shunts are shown and described in U.S. Pat. Nos. 4,167,045 (Sawyer) and 4,712,551 (Rayhanabad). Sawyer teaches a vascular shunt made from Dacron (Registered U.S. Trademark), coated with glutaraldehyde-polymerized proteins, aluminum or other substances. Sawyer also teaches that early attempts to use rigid, gold tubes as vascular shunts were unsuccessful.
Rayhanabad shows a multi-branched vascular shunt for temporary use during surgery. The use of such a shunt enables blood flow to be continued to vital organs even while a main blood vessel is being treated. For permanent implants, it is desirable to utilize a porous material for the shunt or graft to allow for the infiltration of the pores by body tissue in order to firmly hold the shunt or graft in position and to create a shunt or graft formed from living tissue. This need is balanced by the need to provide a liquid-tight conduit to operate as a replacement blood vessel. One approach to balancing these two needs is shown in U.S. Pat. No. 3,106,483 (Kline et al), which acknowledges the prior use of artificial blood vessels formed by knitting, weaving or braiding polymer synthetic filaments such as "Dacron" (Registered U.S. Trademark) or "Teflon" (Registered U.S. Trademark). Use of knitted, woven, or braided implants is said to offer advantages in providing a porous surface into which body tissue may grow after implantation; such implants also offer a secure underlay of suturing. Kline et al teach the use of an assimilatable lining within the graft which initially creates a liquid-tight conduit; the lining thereafter gradually dissolves into the blood stream leaving behind a porous network which by this time has been infiltrated and filled by body tissue to fill the pores and provide a liquid-tight vessel.
U.S. Pat. No. 3,094,762 (Jeckel) teaches the use of Teflon.RTM.knitted or woven into a blood vessel graft. Dardik et al in U.S. Pat. No. 3,974,526, teach the use of the human umbilical cord as a vascular grafting material, including shaping and hardening the cord on a mandrel, chemically treating the umbilical cord to limit antigenicity, and using a reinforcing mesh to strengthen the resulting prosthesis.
The presence or formation of thromboses or blood clots is of significant concern in any surgical procedure, and is also a most serious problem in using arterial-venous shunts or artificial heart valves. Clotting frequently occurs in dialysis shunts, requiring removal of the shunt, clearing and surgical reimplantation. The formation and dislodging of a clot may result in the occlusion or blocking of a blood vessel, interrupting the life-giving flow of blood to major organs of the body. Formation of thromboses in surgically implanted arterial or venous grafts may result because of such factors as the woven, porous nature of the graft material, a construction which may attract blood platelets or debris in the blood stream. The graft's chemical composition, its compliance, and/or its electro-negativity, each of which may evoke a different tissue reaction may also contribute to thrombosis. See, for example, Greisler, et al., "Plasma Polymerized Tetrafluoroethylene/Polyethylene Terephthalate Vascular Prostheses", Arch, Surg. Vol. 124, pp. 967-972 (August, 1989). This creates the attendant risk that once a mass of detritus reaches a significant weight and size, it may adhere to the wall of the blood vessel, progressively blocking the vessel, or it may be dislodged by the flow of blood through the blood vessel and will travel until it encounters a blood vessel having a diameter less than that of the thrombus, causing a blockage.
Prevention of thromboses in implantable shunts has been addressed in U.S. Pat. No. 3,988,782 (Dardik et al) wherein the use of "pre-clotted" or hardened lengths of human umbilical cord as homografts is taught. The anti-thrombogenic properties of such homografts is, according to the patent, a product of the hardening of the umbilical cord length used to manufacture the homograft.
U.S. Pat. No. 4,355,426 (McGregor) teaches the construction of a metallic porous vascular graft, which depends for its anti-thrombogenic properties upon the formation of a smooth coating of tissue created by the growth of nucleated cells from the blood stream over the porous surface and sub-surface of the graft.
Ward et al (U.S. Pat. No. 4,164,524) teach the technique of evacuating gas nuclei trapped in the walls of blood-treatment devices to minimize the presence of cavities within which blood platelets may collect to begin the clotting process.
Outer attempts at limiting the formation of thromboses have utilized coating materials applied to the grafts or shunts. U.S. Pat. No. 4,718,907 (Karwoski et al) teaches the use of a fluorinated coating applied electrically to the surfaces of an interwoven fabric tube. Braun (U.S. Pat. No. 4,265,928) teaches an anti-thrombogenic catheter dependent for its non-clotting properties upon the deposition of a thin coating of an ethylene-acrylic acid copolymer to the interior surface of the catheter.
Yet another approach to limiting the formation of thromboses is to use an anti-clotting agent, such as heparin, in the blood stream of the patient. Use of heparin or any other anti-coagulant has the undesirable side effect of robbing the blood of its ability to clot in the event of a traumatic injury. Attempts have been made to localize the anti-clotting effect of heparin as, for example, in U.S. Pat. No. 4,704,131 (Noishiki et al) who teach the formation of a heparinized collagen to be used as a material for constructing artificial grafts or shunts. Similarly, U.S. Pat. Nos. 4,676,975 and 4,678,660 (McGary et al) teaches the manufacture of anti-thrombogenic thermoplastic incorporating an anti-thrombogenic agent dispersed throughout the material used to construct the graft.
It has long been known that the use of gold in surgical procedures is well-tolerated by the human body because gold is essentially chemically inert, meaning it does not react with such commonly available reagents as sulfur, oxygen, water and the like. Gold is also electrically conductive, a property which may aid in the dispersal of electrical currents that may promote thromboses.
Surgical uses of gold leaf are described in an article entitled "The Use of Charged Gold Leaf in Surgery" authored by Dr. John. P. Gallaher and Dr. Charles F. Geschickter, and published in the Journal of the American Medial Association on Sep. 21, 1964. Drs. Gallagher and Geschickter describe a process well known to all those who have used gold leaf in the painting of signs, namely, the use of a camel's hair brush to impart an electrical charge to the gold leaf and the subsequent application of the gold leaf to a desired surface. It was found that gold was assimilated by the body without adverse reactions and without apparently requiring the use of drugs to control reactions of the body's immune system.
The therapeutic properties of gold, together with the body's long-term tolerance to the presence of gold have been recognized by the medical profession.
For example, the use of gold in the treatment of rheumatoid arthritis is described by D.L. Scott et al. in an article entitled "Combination Therapy With Gold and Hydroxychloroquinine in Rheumatoid Arthritis: a Prospective, Randomized, Placebo Controlled Study" (Br. J. Rheumatology 1989 Apr: 28(2) 128-33).
Gold has also been used in plastic surgery, demonstrating the long term tolerance of tissue for this metal. See, for example, P Chapman, et al., "Results of Upper Lip Loading in the Treatment of Lagophthalmos Caused by Facial Palsy" (Br. J. Plastic Surgery 1988 Jul; 31(4): 369-72); and A.R. Newman, et al., "The Correction of Seventh Nerve Palsy Lagophthalmos with Gold Lid Load" (Ann Plastic Surgery 1988 Feb; 22(2): 142-5).
U.S. Pat. No. 4,054,139 (Crossley) teaches the use of metals such as silver and gold used in catheters to prevent bacterial infection. Such metals are applied in small amounts throughout the material used to form the catheter but Crossley does not suggest the use of a continuous metal coating to present an anti-thrombotic surface for permanent implantation.
U.S. Pat. No. 4,743,253 (Magladry) teaches the application of gold to a metallic compression ring used in a suture ring assembly for heart valves. This is an application which does not address the particular problems of preventing the formation of thromboses on the metallic or rigid portions of the heart valve itself nor on the suture ring and the fabric used to form an anchoring site for the ring. The suture ring of Magladry is ductile and electrically conductive but must be covered by a fabric to form an anchoring site for suturing to the heart.
U.S. Pat. Nos. 4,557,957 and 4,720,400 (Manniso) describe the application of coatings, including metallic coatings, to synthetic non-woven fabric made from polytetrafluoroethylene, a material sold under the trademark GORE-TEX.RTM., which is characterized by nodes interconnected by fibrils, but in such a manner as to narrow or block the interstices formed by such fabric.
It may thus be seen that the characteristics required for the construction of a successfully implantable graft, shunt, patch or valve are the ability of the human body to tolerate the presence of the material from which the implant is formed, the provision of a somewhat porous construction to enable body tissue to infiltrate the implant, thus holding it firmly in place, the resistance of the implant to leaks, particularly where used in a blood vessel subjected to the pressure pluses created by the pumping of blood by the heart and the provision of a mechanism whereby the formation of thromboses within or upon the implant is limited. Such implant should, ideally, be capable of use without requiring anti-coagulant drugs or compounds and should utilize materials which are uniformly non-reactive with body fluid constituents or tissues.
In my experience, many replacement heart valves are manufactured from pyrolitic carbon, and use fabric cuffs (typically Dacron.RTM. or Teflon.RTM.) to surround the suturing ring for use as an attachment site for sutures and, eventually, for infiltration by fibrous tissue. To my knowledge, no valves are presently available which provide gold as a protective coating for the hard surfaces as well as the individual fabric fibers. Such a coating should also ideally be highly electrically conductive to decrease the preserve of electrical currents with a concomitant decrease in the tendency for unwanted cell deposition to occur.
Meeting these criteria is of paramount importance given the rapid development of artificial implantable organs and replacement devices such as heart valves and the like which come into intimate contact with a patient's blood stream. Implants which otherwise function perfectly as replacements for body parts will continue to be unsuitable if such replacements, by their construction, provide sites at which thromboses can form. As discussed above, it has also been learned that the presence of electrical charges and the like provide a breeding ground for the formation of thromboses, and the presence of strength of these currents should be limited or dissipated.
Heretofore, attempted solutions to these problems have focused upon the interaction of blood constituents with the material from which the implants are formed.